Name: pre-conditioning the airways of mice with bleomycin increases the efficiency of orthotopic lung cancer cell engraftment
Uploaded: 2018-06-28T12:30:00
Description: Watch this Scientific Journal Video about Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment at JoVE.com

Deze studie werd gefinancierd door subsidies van het National Cancer Institute (R01CA166376 en R01CA191489 te D.X. Nguyen) en het ministerie van defensie (W81XWH-16-1-0227 te D.X. Nguyen).

Alle experimenten werden uitgevoerd volgens protocollen die zijn goedgekeurd door de institutionele Animal Care en gebruik Comité (IACUC) aan de Yale University.
1. instellen / voorbereiding van de reagentia.
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Bleomycine Let op: Gebaseerd op het wereldwijd geharmoniseerde systeem (GHS) van de indeling en etikettering van chemische stoffen, is Bleomycine geclassificeerd als een gevaar voor de gezondheid van GHS08.<ol>
<li>Bleomycine in een chemische kap voor te be...

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Opvallende klinische parallellen zijn gedocumenteerd tussen longkanker en andere chronische ziekten van de Long-36. Met name patiënten met idiopathische longfibrose (IPF) hebben een verhoogde voorliefde voor ontwikkelende longkanker, en deze vereniging is onafhankelijk van roken geschiedenis37,38. IPF wordt gekenmerkt door progressieve vernietiging van Long architectuur en verminderde ademhalingsfunctie door afzetting van ECM<sup class="x...

Longkanker is de belangrijkste oorzaak van kanker gerelateerde sterfgevallen wereldwijd1. Patiënten met longkanker bezwijken uiteindelijk van metastase tot verre organen, met name aan het centraal zenuwstelsel, lever, bijnieren en botten2,3,4. Thoracale maligniteiten zijn traditioneel ingedeeld als kleincellige longkanker (SCLC) of niet-kleincellige longkanker kanker (NKCLK)5. NKCLK is de meest vaak gediagnosticeerd maligniteit en kan worden onderverdeeld in verschillende histologische subtypes, met inbegrip van adenocarcinoom van de Long (LUAD) en Long plaveiselcelcarcinoom (LUSC)6. Genomic analyse van gereseceerd menselijke primaire longkankerziekten is gebleken dat de tumoren binnen een bepaalde histotype ook divers moleculaire verstoringen, verder bij te dragen aan hun uiteenlopende klinische progressie en verstorende patiënt prognose kunnen uitdrukken. De opmerkelijke heterogeniteit van de longkankerziekten vormt een aanzienlijke uitdaging voor het rationele ontwerp preklinisch onderzoek en uitvoering van effectieve therapeutische strategieën. Daarom is er een noodzaak om uit te breiden van het repertoire van hanteerbare experimentele long kanker modellen te bestuderen van de verschillende cellulaire oorsprong, moleculaire subtypen en stadia van deze ziekte.
Verschillende benaderingen met behulp van dierlijke modellen zijn tewerkgesteld long kanker om te studeren in vivo, elk met hun eigen voor- en nadelen, afhankelijk van de biologische vragen van belang. Genetisch gemodificeerde Muismodellen (GEMMs) kunnen richten op specifieke genetische wijzigingen in een bepaalde voorlopercellen celtype, resulterend in tumoren die vooruitgang binnen een immunocompetent host7. Terwijl zeer krachtig en klinisch relevante, kunnen de latency, variabiliteit, en/of Long tumor morbiditeit geassocieerd met GEMMs verbiedend met bepaalde kwantitatieve metingen en de detectie van late stadium metastase in verre organen8. Een complementaire benadering is het gebruik van allograft modellen, waarbij Long kankercellen, hetzij rechtstreeks uit een muis tumor verkregen of afgeleid eerst als het gevestigde cellijnen in cultuur, opnieuw binnengebracht in syngeneic hosts worden. Naar analogie, zijn long kanker xenografts gevestigd van menselijke cellijnen of patiënt afgeleide tumor monsters. Menselijke cel lijn xenografts of patiënt afgeleide xenografts (PDXs) zijn over het algemeen gehandhaafd bij immuungecompromitteerde muizen en daarom beletten volledig immuun-surveillance9. Ondanks dit nadeel bieden zij een laan voor het doorgeven van de beperking van de hoeveelheid menselijke biospecimens en studie fundamentele in vivo eigenschappen van menselijke kankercellen, die voor meer complexe genomic afwijkingen dan GEMM tumoren coderen.
Een nuttige eigenschap van allografts en xenografts is dat ze vatbaar voor traditionele beperkende cel verdunning testen, werkzaam te kwantificeren van de frequentie van de tumor cellen (TICs) binnen een kwaadaardige cel bevolking10initiëren. In deze experimenten, een bepaald aantal cellen worden subcutaan ingespoten in de flank van de dieren en de frequentie van de TICs kan worden geschat op basis van de tumor te nemen koers. Subcutane tumoren kunnen echter meer hypoxische11 en kunnen niet zeer belangrijke fysiologische beperkingen van de Long tumor communicatie model. Intratracheale levering van epitheliale stam of voorlopercellen in de longen van muizen is een methode om te studeren pulmonaire regeneratie en airway stamcel biologie12. Het tarief van de engraftment van deze techniek kan echter relatief laag, tenzij de longen eerst aan fysiologische vormen van schade, zoals virale infectie13,14 onderworpen zijn. Ondersteuning van inflammatoire stromale cellen en/of de verstoring van het membraan van de kelder Long kan in de cel van de stam van de relevante niches in de distale airways15eigendomsvoorbehoud getransplanteerde cellen verbeteren. Fibrose inducerende agenten kan ook vooraf een voorwaarde van de longen te verbeteren engraftment van geïnduceerde pluripotente cellen16 en17van de mesenchymale stamcellen. Of soortgelijke beschermingsvormen airway letsel kunnen invloed hebben op het engraftment tarief, hebben tumor-initiërende capaciteit, en uitgroei van Long kankercellen nog systematisch worden beoordeeld.
In deze studie beschrijven we een methode te vergroten van de doelmatigheid van orthotopic long kanker cel engraftment, door preconditionering de longen van muizen met blessure. LUAD ontstaat in de distale airways met een grote subset van deze kankers ontwikkelen een fibrotische stroma18 die vaak met slechte prognose19 correleert. Bleomycine, een natuurlijke nonribosomal hybride peptide-polyketide, is uitgebreid om te induceren van longfibrose in muizen20gebruikt. Airway instillation van bleomycine bevordert eerst epitheliale uitputtingsslag in de longblaasjes en rekrutering van ontstekingscellen, met inbegrip van macrofagen, neutrofiele granulocyten en monocyten21. Dit wordt gevolgd door de weefsel remodeling in de distale airways, kelder membraan reorganisatie22,23 en24afzetting extracellulaire matrix (ECM). De effecten van een enkele Bleomycine injectie zijn voorbijgaande, met fibrosis oplossen na 30 dagen in de meeste studies25. Met behulp van zowel allograft en xenograft modellen, we getest als preconditionering de luchtwegen van muizen met bleomycine aanzienlijk van de te nemen koers van LUAD cellen in de longen verhogen kan.

<table>
	<tbody>
		<tr>
			<td>Bleomycin</td>
			<td>Sigma</td>
			<td>B5507-15UN</td>
			<td>CAUTION Health hazard GHS08</td>
		</tr>
		<tr>
			<td>Exel Catheter 24G</td>
			<td>Fisher</td>
			<td>1484121</td>
			<td>Remove needle. For intratracheal injection</td>
		</tr>
		<tr>
			<td>Ketamine (Ketaset inl 100 mg/mL C3N 10 mL)</td>
			<td>Butler Schein</td>
			<td>56344</td>
			<td>To anesthetize mice</td>
		</tr>
		<tr>
			<td>Xylazine</td>
			<td>Butler Schein</td>
			<td>33198</td>
			<td>To anesthetize mice</td>
		</tr>
		<tr>
			<td>Ketoprofen, 5,000 mg</td>
			<td>Cayman Chemical</td>
			<td>10006661</td>
			<td>Analgesic</td>
		</tr>
		<tr>
			<td>Puralube Veterinary Ophthalmic Ointment</td>
			<td>BUTLER ANIMAL HEALTH COMPANY LLC</td>
			<td>8897</td>
			<td>To prevent eye dryness while under anesthesia</td>
		</tr>
		<tr>
			<td>D-Luciferin powder</td>
			<td>Perkin Elmer Health Sciences Inc</td>
			<td>122799</td>
			<td>For luminescent imaging. Reconstitute powder with PBS for a working concentration of 15mg/mL. Protect from Light</td>
		</tr>
		<tr>
			<td>Rodent Intubation stand</td>
			<td>Braintree Scientific</td>
			<td>RIS-100</td>
			<td>Recommended stand for intratracheal injection</td>
		</tr>
		<tr>
			<td>MI-150 ILLUMINATOR 150W MI-150</td>
			<td>DOLAN-JENNER INDUSTRIES</td>
			<td>MI-150 / EEG2823M</td>
			<td>To illuminate and visualize trachea</td>
		</tr>
		<tr>
			<td>Graefe Forceps, 2.75 (7 cm) long serrat</td>
			<td>Roboz</td>
			<td>RS-5111</td>
			<td>For intratracheal injection</td>
		</tr>
		<tr>
			<td>Syringe Luer-Lok Sterile 5ml</td>
			<td>BD / Fisher</td>
			<td>309646</td>
			<td></td>
		</tr>
		<tr>
			<td>Satiny Smooth by Conair Dual Foil Wet/Dry Rechargeable Shaver</td>
			<td>Conair</td>
			<td>-</td>
			<td>To shave mice</td>
		</tr>
		<tr>
			<td>Bonn Scissors, 3.5&#34; straight 15 mm sharp/sharp sure cut blades</td>
			<td>Roboz</td>
			<td>RS-5840SC</td>
			<td></td>
		</tr>
		<tr>
			<td>15 mL conical tube</td>
			<td>BD / Fisher</td>
			<td>352097</td>
			<td></td>
		</tr>
		<tr>
			<td>1.5 mL centrifuge tubes</td>
			<td>USA SCIENTIFIC INC</td>
			<td>1615-5500</td>
			<td></td>
		</tr>
		<tr>
			<td>Vial Scintillation 7 mL Borosilicate Glass GPI</td>
			<td>Fisher</td>
			<td>701350</td>
			<td></td>
		</tr>
		<tr>
			<td>Filter pipette tips (200 &#956;L)</td>
			<td>USA SCIENTIFIC INC</td>
			<td>1120-8710</td>
			<td></td>
		</tr>
		<tr>
			<td>Phosphate Buffered Saline</td>
			<td>Life Technologies</td>
			<td>14190-144</td>
			<td></td>
		</tr>
		<tr>
			<td>0.25% Trypsin-EDTA</td>
			<td>Life Technologies</td>
			<td>25200-056</td>
			<td></td>
		</tr>
		<tr>
			<td>DMEM high glucose</td>
			<td>Life Technologies</td>
			<td>11965-092</td>
			<td></td>
		</tr>
		<tr>
			<td>RPMI Medium 1640</td>
			<td>Life Technologies</td>
			<td>11875-093</td>
			<td></td>
		</tr>
		<tr>
			<td>Fetal bovine serum USDA</td>
			<td>Life Technologies</td>
			<td>10437-028</td>
			<td></td>
		</tr>
		<tr>
			<td>Penicillin-Streptomycin</td>
			<td>Life Technologies</td>
			<td>15140-122</td>
			<td></td>
		</tr>
		<tr>
			<td>Amphotericin B</td>
			<td>Sigma</td>
			<td>A2942-20ML</td>
			<td></td>
		</tr>
		<tr>
			<td>Trypan Blue Stain 0.4%</td>
			<td>Life Technologies</td>
			<td>15250-061</td>
			<td></td>
		</tr>
		<tr>
			<td>Countess Automated Cell Counter</td>
			<td>Life Technologies</td>
			<td>AMQAX1000</td>
			<td></td>
		</tr>
		<tr>
			<td>Flask T/C 75cm sq canted neck, blue cap</td>
			<td>Fisher / Corning</td>
			<td>353135</td>
			<td></td>
		</tr>
		<tr>
			<td>IVIS Spectrum Xenogen Bioluminiscence</td>
			<td>Perkin Elmer Health Sciences Inc</td>
			<td>124262</td>
			<td>For in vivo bioluminescence imaging</td>
		</tr>
		<tr>
			<td>Living image software</td>
			<td>Perkin Elmer Health Sciences Inc</td>
			<td>128113</td>
			<td>For in vivo bioluminescence analysis</td>
		</tr>
		<tr>
			<td>XGI-8 Gas Anesthesia System</td>
			<td>Perkin Elmer Health Sciences Inc</td>
			<td>118918</td>
			<td>For Isoflurane anesthesia</td>
		</tr>
		<tr>
			<td>BD Ultra-Fine II Short Needle Insulin Syringe 1 cc. 31 G x 8 mm (5/16 in)</td>
			<td>BD / Fisher</td>
			<td>BD328418</td>
			<td>For retro-orbital luciferin injection</td>
		</tr>
		<tr>
			<td>Syringe 1ml</td>
			<td>BD / Fisher</td>
			<td>14-823-434</td>
			<td>For intraperitoneal injections</td>
		</tr>
		<tr>
			<td>26 G x 1/2 in. needle</td>
			<td>BD / Fisher</td>
			<td>305111</td>
			<td>For intraperitoneal injections</td>
		</tr>
		<tr>
			<td>4% Paraformaldehyde</td>
			<td>VWR</td>
			<td>43368-9M</td>
			<td>CAUTION Health hazard GHS07, GHS08. For fixing tissue</td>
		</tr>
		<tr>
			<td>Pipet-Lite Pipette, Unv. SL-200XLS+</td>
			<td>METTLER-TOLEDO INTERNATIONAL</td>
			<td>17014411</td>
			<td></td>
		</tr>
		<tr>
			<td>Mayer&#39;s Hematoxylin</td>
			<td>ELECTRON MICROSCOPY SCIENCES</td>
			<td>517-28-2</td>
			<td></td>
		</tr>
		<tr>
			<td>Eosin Y stain 0.25% (w/v) in 57%</td>
			<td>Fisher</td>
			<td>67-63-0</td>
			<td></td>
		</tr>
		<tr>
			<td>Masson Trichrome Stain Kit</td>
			<td>IMEB Inc</td>
			<td>K7228</td>
			<td>For masson trichrome stain to visualize collagen</td>
		</tr>
		<tr>
			<td>Superfrost plus glass slides</td>
			<td>Fisher</td>
			<td>1255015</td>
			<td></td>
		</tr>
		<tr>
			<td>6 well plate</td>
			<td>Corning</td>
			<td>C3516</td>
			<td></td>
		</tr>
		<tr>
			<td>Universal Mycoplasma Detection Kit</td>
			<td>ATCC</td>
			<td>30-1012K</td>
			<td></td>
		</tr>
		<tr>
			<td>OCT Embedding compound</td>
			<td>ELECTRON MICROSCOPY SCIENCES</td>
			<td>62550-12</td>
			<td>For embedding tissue for frozen sections</td>
		</tr>
		<tr>
			<td>Leica CM3050 S Research Cryostat</td>
			<td>Leica</td>
			<td>CM3050 S</td>
			<td>To section tissue for staining analysis</td>
		</tr>
		<tr>
			<td>Keyence All-in One Fluorescence Microscope</td>
			<td>Keyence</td>
			<td>BZ-X700</td>
			<td></td>
		</tr>
		<tr>
			<td>ImageJ</td>
			<td>US National Institutes of Health</td>
			<td>IJ1.46</td>
			<td>http://rsbweb.nih.gov/ij/ download.html</td>
		</tr>
		<tr>
			<td>Prism 7.0 for Mac OS X</td>
			<td>GraphPad Software, Inc.</td>
			<td>-</td>
			<td></td>
		</tr>
		<tr>
			<td>Athymic (Crl:NU(NCr)-Foxn1nu) mice</td>
			<td>Charles River</td>
			<td>NIH-553</td>
			<td></td>
		</tr>
		<tr>
			<td>NSG (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) mice</td>
			<td>Jackson Laboratories</td>
			<td>5557</td>
			<td></td>
		</tr>
		<tr>
			<td>B6129SF1/J mice</td>
			<td>Jackson Laboratories</td>
			<td>101043</td>
			<td></td>
		</tr>
		<tr>
			<td>NIH-H2030 cells</td>
			<td>ATCC</td>
			<td>CRL-5914</td>
			<td></td>
		</tr>
		<tr>
			<td>368T1</td>
			<td>generously provided by Monte Winslow (Standford University)</td>
			<td>-</td>
			<td></td>
		</tr>
		<tr>
			<td>PC9 cells</td>
			<td>Nguyen DX et al. Cell. 2009;138:51&#8211;62</td>
			<td>-</td>
			<td></td>
		</tr>
		<tr>
			<td>H2030 BrM3 cells</td>
			<td>Nguyen DX et al. Cell. 2009;138:51&#8211;62</td>
			<td>-</td>
			<td></td>
		</tr>
	</tbody>
</table>

pre-conditioning the airways of mice with bleomycin increases the efficiency of orthotopic lung cancer cell engraftment

Longkanker is een dodelijke behandeling vuurvaste ziekte die biologisch heterogeen is. Om te begrijpen en effectief behandelen het volledige klinische spectrum van thoracale maligniteiten, zijn extra dierlijke modellen die diverse menselijke long kanker subtypen en stadia kunnen recapituleren nodig. Allograft of xenograft modellen zijn veelzijdig en inschakelen van de kwantificering van tumorigene capaciteit in vivo, met behulp van kwaadaardige cellen van lymfkliertest of menselijke oorsprong. Echter zijn eerder beschreven methoden voor long kanker cel engraftment uitgevoerd in niet-fysiologische sites, zoals de flank van muizen, te wijten aan de inefficiëntie van orthotopic transplantatie van cellen in de longen. In deze studie beschrijven we een methode ter verbetering van orthotopic long kanker cel engraftment door preconditionering de luchtwegen van muizen met de fibrose inducerend agent bleomycine. Als een experiment van proof-of-concept, wij deze aanpak om het engraft van tumorcellen van het Long adenocarcinoom subtype, verkregen uit de muis of menselijke bronnen, in verschillende muizenstammen toegepast. We laten zien dat het verwonden van de luchtwegen met bleomycine vóór tumor cel injectie de engraftment van tumorcellen van 0-17 verhoogt % tot 71-100%. Deze methode verbeterde aanzienlijk, Long tumor incidentie en verdere uitgroei met behulp van verschillende modellen en muis stammen. Daarnaast verspreiden werk Long kankercellen uit de longen in relevante verre organen. Dus, wij bieden een protocol dat kan worden gebruikt om te stellen en onderhouden van nieuwe modellen van de orthotopic van longkanker met beperking van de hoeveelheid cellen of biospecimen en kwantitatief beoordelen de tumorigene capaciteit van Long kankercellen in fysiologisch relevante instellingen .

Het vergroten van de efficiëntie van LUAD kanker cel engraftment in de longen van muizen, ontwikkelden we een protocol dat eerst vooraf de voorwaarden van de luchtwegen met behulp van bleomycine gevolgd door orthotopic tumor cel injectie (Figuur 1). We hebben bevestigd dat zelfs indien toegediend in immuungecompromitteerde athymic muizen, bleomycine voorbijgaande fibrose geïnduceerd door dag 14 blijkens door verlies van airway architectuur en verhoogde coll...

Watch this Scientific Journal Video about Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment at JoVE.com

Pre-Conditioning the Airways of Mice with Bleomycin Increases the Efficiency of Orthotopic Lung Cancer Cell Engraftment

Beschrijven we een methode om engraftment van de orthotopic van longkanker kankercellen in de longen lymfkliertest aanzienlijk te verbeteren door preconditionering van de luchtwegen met blessure. Deze benadering kan ook worden toegepast om te studeren stromale interacties binnen de longen communicatie, gemetastaseerde verspreiding, long kanker co morbiditeit en efficiënter genereren patiënt afgeleid xenografts.

Preconditionering de luchtwegen van muizen met bleomycine verhoogt de efficiëntie van Orthotopic long kanker cel Engraftment

Lung cancer is a deadly treatment refractory disease that is biologically heterogeneous. To understand and effectively treat the full clinical spectrum of ...

The overall goal of this procedure is to increase the efficiency of transplanting tumor-initiating lung cancer cells into the airways of mice. This method can help establish new preclinical models in order to answer key questions in cancer biology, including the causes of drug resistance and relationship between fibrosis and lung cancer. The main advantage of this technique is that it increase the transplantation efficiency of tumor-initiating cells into the lungs of a variety of mouse strains.The implications of this technique extend toward therapy, because it enables us to model a greater variety of human lung cancer subtypes, known to have different clinical responses to treatment. For this protocol, the mice must first be injected with bleomycin. Then, after 14 days, the tumor cells are injected.The procedure for both injections is very similar and described here. Two hours prior to the injection, thaw the bleomycin stock on ice and dilute it to the working concentration. Keep it on ice.For a cell bolus, have a cell suspension prepared as described in the text protocol. The procedure time for each mouse is about 10 minutes all together. Be certain to confirm proper anesthesia using a toe pinch, and apply vet ointment to the eyes.At this time, if the mouse has dark hair, then shave the entire rib area both ventrally and dorsally so it can be imaged correctly. Then, place the mouse on the intubation platform by securing it by its front teeth with it's back against the platform. If a cell bolus is to be injected, resuspend it now with gentle trituration.Now illuminate the upper-chest region, open the mouth, and gently pull out the tongue using flat forceps. Prepare an IV catheter for the trachea by removing the needle, then position it over the tracheal opening. Next, insert the catheter into the trachea until the top of the catheter is near the front teeth and illuminate the interior of the catheter to confirm its placement.Then, dispense the 50 microliters of freshly made bleomycin, or cell suspension, directly into the catheter. Wait a few seconds for the entire volume to travel down the catheter. Then, remove the catheter and dispose of it in 10%bleach.If the mouse is not inhaling the liquid, carefully monitor its breathing and adjust the catheter position. If the mouse stops breathing, immediately remove the catheter and allow the mouse to breath before you reinsert the catheter in. After removing the catheter, continue performing the procedure to have five treated mice, still anesthetized, and ready to image.For recovery, place the mouse supine on an IACUC approved heating pad in a recovery cage and monitor it until it has fully recovered. Two or three minutes after injecting the cells, inject 100 microliters of luciferin retro-orbitally, using an insulin needle. Alternate the eye used for injection every imaging session.After waiting at lest two minutes, position up to five mice in an animal bioluminescence imager, in the sternal recumbency position and acquire a dorsal picture using luminescence settings. Under the control panel, adjust the resolution and sensitivity settings, to measure the luminescence of the cells. For most applications, start with three minutes, set the binning to medium, set the f/stop to one, set the field of view to d, and set the subject height to 1.5.If the injection was successful, a signal is detected in the upper chest area in one lung or both lungs. If cells are clustered at the entrance of the trachea, the injection was unsuccessful. After taking the dorsal image, flip the mice and acquire a ventral image and adjust the setting as needed.After imaging, proceed with postoperative care as described in the text protocol. Then, repeat this imaging protocol three days post-engraftment and weekly thereafter. To analyze the images, use a bioluminescence analysis software.First, load all the appropriate images in the series. This section is detailed to one software package. Next, for each mouse, in the first image of the series, create a square region of interest and position it over the upper chest area covering the entire lung region.Then, using a right click, access the copy all regions of interest function, and use this tool to apply the same regions of interest to each image in the group. Then, within each image, tweak the positions of the squares to cover the upper chest of each mouse. Do this for both the ventral and dorsal views.Now, in the upper left corner of the image window, select the photons function. Then select the measure option. The data from the regions of interest is then displayed in an output table as total flux.Analyze this data as needed. When immune compromised, athymic mice were treated with bleomycin. Prior to cell-bolus engraftment, transient fibrosis was observed by day 14 in bleomycin-treated mice, but not vehicle-treated mice.Next, cells from the established human lung cancer cell line, H2030, were delivered intratracheally into the lungs of these mice. After 35 days, bleomycin-treated mice had a high lung-tumor burden. However, in vehicle treated animals, no tumors were detected.The lung-tumor burden was confirmed using histology. Lungs pretreated with vehicle had no evidence of tumor nodules, whereas bleomycin pretreated lungs had large tumor nodules. After transplanting a metastatic H2030 BrM 3 cell line, by 39 to 57 days, bioluminescence was too intense for imaging, so metastasis was analyzed in distant organs ex vivo.Small lesions could be detected in various tissues, suggesting that this method holds promise, to study spontaneously disseminated disease. Once mastered, this technique can be done in 10 minutes per cage of five mice without imaging and 20 minutes per cage when also imaging the mice. While attempting this procedure, it is important to remember to ensure proper insertion of the catheter and to monitor the animal's breathing.Following this procedure, other methods like pharmacological studies or aminoacetic chemistry of harvested tissue can be performed in order to answer additional questions, like how engrafted tumors respond to drugs or characterizing tumor stromal interactions specific to the lungs. After its development, this technique can be applied to different mouse strains and tumor models, including patient-derived xenografts in a physiologically relevant setting. Don't forgot that working with bleomycin can be extremely hazardous and precautions such as manipulation in a biohazard hood and proper disposal should always be taken while performing this procedure.

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Niet-invasieve evaluatie van de werkzaamheid van nieuwe therapieën voor Intestinale Pathologieën gebruik van een serieel Endoscopische Imaging van levende muizen

Animal models of inflammatory bowel disease (IBD) and colorectal cancer (CRC) have provided significant insight into the cell intrinsic and extrinsic ...

Cardiac Catheterization in Mice to Measure the Pressure Volume Relationship: Investigating the Bowditch Effect

Hartkatheterisatie in Muizen bij de Pressure Volume Relationship Meet: Onderzoek naar de Bowditch Effect

Animal models that mimic human cardiac disorders have been created to test potential therapeutic strategies. A key component to evaluating these ...

A "Patient-Like" Orthotopic Syngeneic Mouse Model of Hepatocellular Carcinoma Metastasis

Een &quot;Patiënt-Like&quot; Orthotope Syngene Mouse Model van Hepatocellular carcinoom metastase

The majority of cancer-related deaths are caused by the metastasis of the cancer rather than the primary tumor itself. Yet, the underlying mechanisms of ...